- Email: [email protected]
Rare Primary Pleomorphic Adenoma in Posterior Fossa
Case Report
Rare Primary Pleomorphic Adenoma in Posterior Fossa Liqun Yang1, Leong Tan2, Queenie Lau3, Rumal Jayalath4
Key words Heterotopia - Pleomorphic adenoma - Salivary gland -
Abbreviations and Acronyms CN: Cranial nerve CNS: Central nervous system CT: Computed tomography MRI: Magnetic resonance imaging From the Departments of 1Neurosurgery and 3Pathology, Gold Coast University Hospital, Southport; 2Department of Neurosurgery, Pindara Private Hospital, Benowa; and 4 Department of Neurosurgery, Princess Alexandria Hospital, Brisbane, Queensland, Australia To whom correspondence should be addressed: Liqun Yang, Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 93:484.e5-484.e8. http://dx.doi.org/10.1016/j.wneu.2016.07.059 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter Crown Copyright ª 2016 Published by Elsevier Inc. All rights reserved.
- BACKGROUND:
Pleomorphic adenoma is a benign neoplastic tumor of the salivary gland. Salivary gland tumors in the intracranial cavity are generally restricted to the pituitary gland and sellar region. To our knowledge, there has been only 1 previous case report of a primary central nervous system pleomorphic adenoma outside of the sellar region. In that case report of a posterior fossa pleomorphic adenoma, typical myxochondroid stroma was not identified on histology, and its pathogenesis was not explored.
- CASE
DESCRIPTION: A 71-year-old woman presented with a 6-week history of occipital headache and unsteadiness. Contrast-enhanced computed tomography and magnetic resonance imaging studies revealed a solitary large posterior fossa tumor in the left cerebellopontine angle measuring 47 3 43 3 45 mm. The tumor resulted in moderate hydrocephalus and significant mass effect with compression of the pons and medulla. She underwent a stereotactic right ventriculoperitoneal shunt insertion followed by a stereotactic craniotomy and complete excision of the tumor. The operation went uneventfully, and the patient had an uncomplicated recovery. Histopathologic examination revealed a benign pleomorphic adenoma (benign salivary gland tumor) with a classic appearance comprising an admixture of ductal epithelial cells, myoepithelial elements, and nodules of myxochondroid stroma. No extracranial source has been identified despite extensive investigation and 8 years of follow-up.
- CONCLUSIONS:
INTRODUCTION Pleomorphic adenoma is a benign neoplastic tumor of the salivary gland.1,2 It is the most common neoplasm of the salivary gland,3,4 accounting for approximately 65% of all salivary gland neoplasms and 70%e80% of all benign tumors of the major salivary glands.5 Of pleomorphic adenomas, 65%e85% arise in the parotid gland; 8% arise in the submandibular gland; and only 6%e7% arise in the minor salivary glands of the oral cavity, nasal cavity, and paranasal sinuses.4 It is usually solitary and manifests as a painless, slow-growing, well-demarcated nodular mass in middle-aged patients.5 It can recur after resection and invade normal adjacent tissue.6 Although it is classified as a benign tumor, pleomorphic adenomas may undergo malignant transformation to form carcinoma ex pleomorphic adenoma.5 Metastasis of a benign pleomorphic adenoma without malignant transformation, also known as metastasizing pleomorphic adenoma, is rare. Bone, lung, and lymph nodes are
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This case study illustrates a classic primary central nervous system pleomorphic adenoma in an unusual intracranial site. Its pathogenesis is postulated to involve salivary gland heterotopia.
the most common sites of metastatic disease.7 Cranial metastasis is very rare.5,8 Patients with metastasizing pleomorphic adenoma invariably have a history of having a pleomorphic adenoma removed, and they typically have had multiple recurrences before metastatic involvement.5,8 In this report, we describe an unusual case of a primary posterior cranial fossa classic pleomorphic adenoma in a 71-year-old woman with no previous history of salivary gland neoplasia and no other lesions identified despite extensive investigations. An 8-year followup examination showed no extracranial source and no recurrence of the tumor. Primary central nervous system (CNS) pleomorphic adenoma was first reported by Yano et al.9 in 1997. To the best of our knowledge, our case study is the second case report of a primary CNS pleomorphic adenoma outside of the sellar region and
the only one with unequivocal classic histologic features. We also review the literature and discuss the possibility of salivary gland heterotopia as its pathogenesis. This represents a case of a classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site. CASE REPORT History and Examination A 71-year-old woman presented with a 6week history of occipital headache and unsteadiness. She remained well otherwise and had no significant past medical history. On examination, she was unsteady on her feet and tended to veer to the left. Romberg signs were negative. There were no other abnormal neurologic signs, including intact cranial nerve (CN) V, CN VII, and CN VIII. A contrast-enhanced computed tomography (CT) scan of the
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.07.059
CASE REPORT LIQUN YANG ET AL.
head revealed a well-circumscribed mass lesion in the left posterior fossa. Magnetic resonance imaging (MRI) studies confirmed a solitary large posterior fossa tumor in the left cerebellopontine angle (Figure 1AeC). It measured 47 43 45 mm. There was no compromise of the adjacent transverse or sigmoid sinuses. The tumor resulted in moderate hydrocephalus and significant mass effect with compression of the pons and medulla. Operation and Postoperative Course The patient first underwent a stereotactic right ventriculoperitoneal shunt insertion for obstructive hydrocephalus, as the shunting procedure is a safe and effective option to allow gradual normalization of intracranial hypertension with a low risk of intraperitoneal tumor dissemination.10,11 A postoperative CT scan of the head confirmed the shunt was in a satisfactory position. She was then readmitted 2 weeks later for a stereotactic craniotomy (unilateral left suboccipital approach) and resection of the large posterior fossa tumor. During the operation, the tumor was noted to have a fibrous consistency and was found to arise intradurally in the left cerebellopontine angle. It was attached to
RARE PRIMARY PLEOMORPHIC ADENOMA IN POSTERIOR FOSSA
the adjacent petrous ridge just posterior to the petrosal vein (porus acusticus). CN VII and CN VIII were found anterior to the tumor and were visualized and preserved. CN V was not seen because this tumor was posterior and superior to the petrosal vein. This finding explains why CN V, CN VII, and CN VIII were intact on examination. The tumor was completely excised, and she made a good recovery postoperatively. A postoperative CT scan of the head was satisfactory and confirmed total resection of the tumor. After the operation, her gait remained unsteady, for which she underwent intensive rehabilitation. At the 6month follow-up examination, her gait had recovered completely, and MRI of the head was satisfactory. She was assessed by an ear, nose, and throat surgeon for further investigations to look for a possible primary source of the salivary gland tumor. No primary lesion has been identified despite extensive examination and investigations, including salivary gland ultrasound; CT scan of the chest, abdomen, and pelvis; MRI of the head and neck; and positron emission tomography scan. She was evaluated in April 2016, 8 years after her surgery, and no evidence was found of extracranial lesion and
Figure 1. Neuroimaging. (AeC) Preoperative magnetic resonance imaging T1-weighted sequences with gadolinium (axial, coronal, and sagittal views) revealed a 4.7 4.3 4.5 cm posterior fossa tumor in the left cerebellopontine angle with marked mass effect and moderate hydrocephalus. The tumor demonstrates heterogeneous but prominent enhancement. (DeF) Follow-up magnetic resonance imaging T1-weighted
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intracranial recurrence on brain MRI (Figure 1DeF). She is currently still working as a part-time cleaner at the age of 78. Histopathologic Findings Formalin-fixed, paraffin-embedded hematoxylin-eosinestained sections of the tissue specimen revealed a partially encapsulated tumor composed of duct-like structures admixed with myxochondroid stroma (Figure 2). The ducts were lined by inner luminal cuboidal to columnar epithelial cells and surrounded by an abluminal layer of myoepithelial cells. Occasional mucous cells were also present in the lining epithelium of the ducts. Luminal eosinophilic secretory material was seen (Figure 3A). There was an intimate association of the duct-like structures with the myxochondroid stroma; aggregates of plasmacytoid myoepithelial cells were seen to spread from the environs of the duct-like structures and “melt” into the adjacent stroma (Figure 3B). No carcinomatous change was seen. Tongues of tumor protruded into the capsule, and the capsule was deficient in other areas. Immunohistochemistry demonstrated strong staining of the inner
sequences with gadolinium (axial, coronal, and sagittal views) obtained 8 years after surgery show the tumor has been completely resected with no evidence of recurrence. There was an artifact obscuring some of the right cerebellum secondary to the presence of a ventriculoperitoneal shunt over the right occipital bone.
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myoepithelial nature (Figure 3D), and the luminal ductal epithelial cells were appropriately negative. Because of the unusual intracranial location of the tumor, an additional opinion on the case was sought, and the slides of the pathologic specimens were discussed at a slide seminar in a national neuropathology conference in Sydney, Australia. The consensus review confirmed that it was a benign pleomorphic adenoma. Figure 2. Photomicrograph of the surgical specimen. The pleomorphic tumor is composed of an admixture of duct-like structures and nodules of myxochondroid stroma. A fragment of normal cerebellum is present in the lower right corner. (Hematoxylin-eosin, 20.)
luminal ductal epithelial cells by CAM5.2 (Figure 3C) and epithelial membrane antigen, whereas the cells within the outer layer were predominantly negative. Smooth muscle actin, calponin, and cytokeratin 14 highlighted the outer layer of the ductal structures, confirming their
DISCUSSION Pleomorphic adenoma is the most common benign salivary gland neoplasm.12-14 It is also known as a benign mixed tumor, salivary gland type, with classic histologic composition of a mixture of cells derived from the salivary gland ductal apparatus and stroma.5 In this case, the tumor displayed its typical pleomorphic nature and was characterized by an admixture of ductal epithelial and myoepithelial elements in a variable background stroma that was mucoid and
Figure 3. Photomicrographs of the surgical specimen. (A) Ductal structures lined by an inner luminal layer of cuboidal to columnar epithelial cells and surrounded by an outer layer of myoepithelial cells. Occasional mucous cells are also present in the lining, and luminal eosinophilic secretions are present. (Hematoxylin-eosin, 200.) (B) Typical intimate association of the duct-like structures with the myxochondroid stroma with aggregates of myoepithelial cells “melting” into the adjacent stroma. (Hematoxylin-eosin, 100.) (C) Immunohistochemistry for CAM5.2 demonstrated strong staining of luminal ductal epithelial cells, but the outer layer is predominantly negative. (CAM5.2, 200.) (D) Smooth muscle actin highlighted the outer layer of cells only, confirming its myoepithelial nature. (Smooth muscle actin, 200.)
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cartilaginous. There was no mitotic activity or cytologic or architectural atypia to suggest malignant transformation. Despite extensive investigations, no extracranial source has been identified at 8 years after the operation. Metastasis of a benign pleomorphic adenoma is extremely rare.5,8 The metastatic foci are histologically identical to the primary benign tumor and do not show clinical or histologic features commonly associated with malignant neoplasms.8,14 Tumor recurrence at the primary site characteristically precedes metastasizing pleomorphic adenomas, occurring in approximately 90% of the cases.12-14 Few cases of metastases without local recurrence have been reported in the literature. Bone, lung, and lymph nodes are the most common sites of metastatic disease, but involvement of kidney, liver, CNS, retroperitoneum, and skin has also been rarely reported.7,14 The initial placement of ventriculoperitoneal shunt in this case is based on considerations that the shunting procedure is a safe and effective option to allow gradual normalization of her intracranial hypertension and allow sufficient time for preoperative work-up. The risk of shunt acting as a conduit for extraneural metastases is very low.10,11 In the present case, the patient had no previous surgical history, and extensive radiologic investigations revealed no extracranial lesion. She has been followed for 8 years with satisfactory medical imaging and excellent clinical outcomes. This represents a case of a primary classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site, as primary salivary gland tumors in the intracranial cavity are almost always restricted to the pituitary gland and sellar region because of the presence of Rathke cleft remnants, which may develop into heterotopic salivary gland rests.15 There have been only 4 isolated case reports in the literature of primary salivary gland tumors within the intracranial cavity outside the sellar region.9,16-18 Pleomorphic adenoma is the most common benign salivary gland tumor.12-14 To the best of our knowledge, there has been only 1 previous case report of a primary CNS pleomorphic adenoma, by Yano et al.9 in 1997, who described a posterior cranial fossa pleomorphic adenoma. Their case did not
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.07.059
CASE REPORT LIQUN YANG ET AL.
demonstrate the presence of the classic myxochondroid stroma on histology, and its pathogenesis was not elucidated. There has been no second report on primary CNS pleomorphic adenoma and no previous reports with classic histologic appearances of a pleomorphic adenoma. It is postulated that salivary gland heterotopia is the likely pathogenetic mechanism in the development of rare salivary gland tumors in an unusual intracranial location. One hypothesis is that major and minor salivary glands arise in the embryo from invaginations of the primitive oral epithelium, and the ectopic salivary gland tissue may develop from vestigial structures derived from primitive oral epithelium, such as Rathke pouch, whose cleft remnants can be found in the sellar region.15 Other theories explaining the development of heterotopic salivary gland rests include dislocation of intact seromucous glands from oral cavity and induction of pituitary epithelium by salivary gland mesenchyme accompanying Rathke pouch during embryogenesis (heteroplasia).16 Outside of these locations, intracranial salivary gland rests are rare.16,18 It has been observed that during embryogenesis, thickened patches of ectoderm (known as epibranchial placodes), adjacent to CNs, maintained a close relationship with CN VII.16 It has been hypothesized that some vesicles derived from the epibranchial placodes at the dorsal aspect of the first and second pharyngeal arches may have become dislodged and migrated with the elongation of the facial nerve and its chorda tympani branch to differentiate later into salivary gland tissue in the cerebellopontine angle.16 It has been reported that 26 cases of heterotopic salivary gland tissue and 1 pleomorphic adenoma within the middle ear (also derived from the branchial apparatus) were noted to have mostly an intimate relationship with the facial nerve and chorda tympani branch,19-22 further supporting the aforementioned hypothesis. Additionally, given its proximity to the middle ear, salivary tissue in mastoid air cells may become dislocated and subsequently migrate into posterior cranial fossa.16,18
RARE PRIMARY PLEOMORPHIC ADENOMA IN POSTERIOR FOSSA
CONCLUSIONS Our case study demonstrates that primary pleomorphic adenoma and salivary gland neoplasms may rarely occur in the CNS, and the pathogenesis may involve salivary gland heterotopia. This is a case of a classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site and illustrates the complexity of head and neck anatomy and its embryologic assemblage. REFERENCES 1. Cresson DH, Goldsmith M, Askin FB, Reddick RL, Postma DS, Siegal GP. Metastasizing pleomorphic adenoma with myoepithelial cell predominance. Pathol Res Pract. 1990;186:795-800 [discussion: 801-802]. 2. Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G. Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope. 2001;111: 2195-2200. 3. Gnepp DR, Brandwein MS, Henley JD. Salivary and lacrimal glands. In: Gnepp DR, ed. Diagnostic Surgical Pathology of the Head and Neck. Philadelphia, PA: Saunders; 2001:325-430. 4. Som PM, Brandwein MS. Salivary glands: anatomy and pathology. In: Som PM, Curtin HD, eds. Head and Neck Imaging. St Louis, MO: Mosby; 2003: 2067-2076. 5. Sheedy SP, Welker KM, DeLone DR, Gilbertson JR. CNS metastases of carcinoma ex pleomorphic adenoma of the parotid gland. AJNR Am J Neuroradiol. 2006;27:1483-1485. 6. Leonetti JP, Marzo SJ, Petruzzelli GJ, Herr B. Recurrent pleomorphic adenoma of the parotid gland. Otolaryngol Head Neck Surg. 2005;133:319-322. 7. Morrison PD, McMullin JP. A case of metastasizing benign pleomorphic adenoma of the parotid. Clin Oncol. 1984;10:173-176. 8. Fujimura M, Sugawara T, Seki H, Otawara Y, Sakuma T, Nakano Y, et al. Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor of the salivary gland—case report. Neurol Med Chir (Tokyo). 1997;37:546-550. 9. Yano H, Funakoshi T, Shinoda J, Sakai N, Kokuzawa G, Shimokawa K. Primary pleomorphic adenoma in posterior cranial fossa. Brain Tumor Pathol. 1997;14:75-78.
primary central nervous J Neurosurg. 1991;74:872-877.
system
tumours.
12. Freeman SB, Kennedy KS, Parker GS, Tatum SA. Metastasizing pleomorphic adenoma of the nasal septum. Arch Otolaryngol Head Neck Surg. 1990;116: 1331-1333. 13. Pitman MB, Thor AD, Goodman ML, Rosenberg AE. Benign metastasizing pleomorphic adenoma of salivary gland: diagnosis of bone lesions by fine-needle aspiration biopsy. Diagn Cytopathol. 1992;8:384-387. 14. Wenig BM, Hitchcock CL, Ellis GL, Gnepp DR. Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis. Am J Surg Pathol. 1992;16:845-858. 15. Hampton TA, Scheithauer BW, Rojiani AM, Kovacs K, Horvath E, Vogt P. Salivary gland-like tumors of the sellar region. Am J Surg Pathol. 1997;21:424-434. 16. Curry B, Taylor CW, Fisher AW. Salivary gland heterotopia: a unique cerebellopontine angle tumor. Arch Pathol Lab Med. 1982;106:35-38. 17. Erdogan S, Rodriguez FJ, Scheithauer BW, AbellAleff PC, Rabin M. Malignant myoepithelioma of cranial dura. Am J Surg Pathol. 2007;31:807-811. 18. Rodriguez F, Scheithauer BW, Ockner DM, Giannini C. Solitary fibrous tumor of the cerebellopontine angle with salivary gland heterotopia: a unique presentation. Am J Surg Pathol. 2004;28:139-142. 19. Enoz M, Suoglu Y. Salivary gland choristoma of the middle ear. Laryngoscope. 2006;116:1033-1034. 20. Hinni ML, Beatty CW. Salivary gland choristoma of the middle ear: report of a case and review of the literature. Ear Nose Throat J. 1996;75:422-424. 21. Lee DK, Kim JH, Cho YS, Chung WH, Hong SH. Salivary gland choristoma of the middle ear in an infant: a case report. Int J Pediatr Otorhinolaryngol. 2006;70:167-170. 22. Saeed YM, Bassis ML. Mixed tumor of the middle ear. A case report. Arch Otolaryngol. 1971;93: 433-434.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 8 May 2016; accepted 15 July 2016
10. Nigim F, Critchlow J, Kasper E. Role of ventriculoperitoneal shunting in patients with neoplasms of the central nervous system. Mol Clin Oncol. 2015;3:1381-1386.
Citation: World Neurosurg. (2016) 93:484.e5-484.e8. http://dx.doi.org/10.1016/j.wneu.2016.07.059
11. Berger MS, Baumeister B, Geyer JR. The risks of metastases from shunting in children with
1878-8750/$ - see front matter Crown Copyright ª 2016 Published by Elsevier Inc. All rights reserved.
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Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
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Rare Primary Pleomorphic Adenoma in Posterior Fossa Liqun Yang1, Leong Tan2, Queenie Lau3, Rumal Jayalath4
Key words Heterotopia - Pleomorphic adenoma - Salivary gland -
Abbreviations and Acronyms CN: Cranial nerve CNS: Central nervous system CT: Computed tomography MRI: Magnetic resonance imaging From the Departments of 1Neurosurgery and 3Pathology, Gold Coast University Hospital, Southport; 2Department of Neurosurgery, Pindara Private Hospital, Benowa; and 4 Department of Neurosurgery, Princess Alexandria Hospital, Brisbane, Queensland, Australia To whom correspondence should be addressed: Liqun Yang, Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 93:484.e5-484.e8. http://dx.doi.org/10.1016/j.wneu.2016.07.059 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter Crown Copyright ª 2016 Published by Elsevier Inc. All rights reserved.
- BACKGROUND:
Pleomorphic adenoma is a benign neoplastic tumor of the salivary gland. Salivary gland tumors in the intracranial cavity are generally restricted to the pituitary gland and sellar region. To our knowledge, there has been only 1 previous case report of a primary central nervous system pleomorphic adenoma outside of the sellar region. In that case report of a posterior fossa pleomorphic adenoma, typical myxochondroid stroma was not identified on histology, and its pathogenesis was not explored.
- CASE
DESCRIPTION: A 71-year-old woman presented with a 6-week history of occipital headache and unsteadiness. Contrast-enhanced computed tomography and magnetic resonance imaging studies revealed a solitary large posterior fossa tumor in the left cerebellopontine angle measuring 47 3 43 3 45 mm. The tumor resulted in moderate hydrocephalus and significant mass effect with compression of the pons and medulla. She underwent a stereotactic right ventriculoperitoneal shunt insertion followed by a stereotactic craniotomy and complete excision of the tumor. The operation went uneventfully, and the patient had an uncomplicated recovery. Histopathologic examination revealed a benign pleomorphic adenoma (benign salivary gland tumor) with a classic appearance comprising an admixture of ductal epithelial cells, myoepithelial elements, and nodules of myxochondroid stroma. No extracranial source has been identified despite extensive investigation and 8 years of follow-up.
- CONCLUSIONS:
INTRODUCTION Pleomorphic adenoma is a benign neoplastic tumor of the salivary gland.1,2 It is the most common neoplasm of the salivary gland,3,4 accounting for approximately 65% of all salivary gland neoplasms and 70%e80% of all benign tumors of the major salivary glands.5 Of pleomorphic adenomas, 65%e85% arise in the parotid gland; 8% arise in the submandibular gland; and only 6%e7% arise in the minor salivary glands of the oral cavity, nasal cavity, and paranasal sinuses.4 It is usually solitary and manifests as a painless, slow-growing, well-demarcated nodular mass in middle-aged patients.5 It can recur after resection and invade normal adjacent tissue.6 Although it is classified as a benign tumor, pleomorphic adenomas may undergo malignant transformation to form carcinoma ex pleomorphic adenoma.5 Metastasis of a benign pleomorphic adenoma without malignant transformation, also known as metastasizing pleomorphic adenoma, is rare. Bone, lung, and lymph nodes are
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This case study illustrates a classic primary central nervous system pleomorphic adenoma in an unusual intracranial site. Its pathogenesis is postulated to involve salivary gland heterotopia.
the most common sites of metastatic disease.7 Cranial metastasis is very rare.5,8 Patients with metastasizing pleomorphic adenoma invariably have a history of having a pleomorphic adenoma removed, and they typically have had multiple recurrences before metastatic involvement.5,8 In this report, we describe an unusual case of a primary posterior cranial fossa classic pleomorphic adenoma in a 71-year-old woman with no previous history of salivary gland neoplasia and no other lesions identified despite extensive investigations. An 8-year followup examination showed no extracranial source and no recurrence of the tumor. Primary central nervous system (CNS) pleomorphic adenoma was first reported by Yano et al.9 in 1997. To the best of our knowledge, our case study is the second case report of a primary CNS pleomorphic adenoma outside of the sellar region and
the only one with unequivocal classic histologic features. We also review the literature and discuss the possibility of salivary gland heterotopia as its pathogenesis. This represents a case of a classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site. CASE REPORT History and Examination A 71-year-old woman presented with a 6week history of occipital headache and unsteadiness. She remained well otherwise and had no significant past medical history. On examination, she was unsteady on her feet and tended to veer to the left. Romberg signs were negative. There were no other abnormal neurologic signs, including intact cranial nerve (CN) V, CN VII, and CN VIII. A contrast-enhanced computed tomography (CT) scan of the
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.07.059
CASE REPORT LIQUN YANG ET AL.
head revealed a well-circumscribed mass lesion in the left posterior fossa. Magnetic resonance imaging (MRI) studies confirmed a solitary large posterior fossa tumor in the left cerebellopontine angle (Figure 1AeC). It measured 47 43 45 mm. There was no compromise of the adjacent transverse or sigmoid sinuses. The tumor resulted in moderate hydrocephalus and significant mass effect with compression of the pons and medulla. Operation and Postoperative Course The patient first underwent a stereotactic right ventriculoperitoneal shunt insertion for obstructive hydrocephalus, as the shunting procedure is a safe and effective option to allow gradual normalization of intracranial hypertension with a low risk of intraperitoneal tumor dissemination.10,11 A postoperative CT scan of the head confirmed the shunt was in a satisfactory position. She was then readmitted 2 weeks later for a stereotactic craniotomy (unilateral left suboccipital approach) and resection of the large posterior fossa tumor. During the operation, the tumor was noted to have a fibrous consistency and was found to arise intradurally in the left cerebellopontine angle. It was attached to
RARE PRIMARY PLEOMORPHIC ADENOMA IN POSTERIOR FOSSA
the adjacent petrous ridge just posterior to the petrosal vein (porus acusticus). CN VII and CN VIII were found anterior to the tumor and were visualized and preserved. CN V was not seen because this tumor was posterior and superior to the petrosal vein. This finding explains why CN V, CN VII, and CN VIII were intact on examination. The tumor was completely excised, and she made a good recovery postoperatively. A postoperative CT scan of the head was satisfactory and confirmed total resection of the tumor. After the operation, her gait remained unsteady, for which she underwent intensive rehabilitation. At the 6month follow-up examination, her gait had recovered completely, and MRI of the head was satisfactory. She was assessed by an ear, nose, and throat surgeon for further investigations to look for a possible primary source of the salivary gland tumor. No primary lesion has been identified despite extensive examination and investigations, including salivary gland ultrasound; CT scan of the chest, abdomen, and pelvis; MRI of the head and neck; and positron emission tomography scan. She was evaluated in April 2016, 8 years after her surgery, and no evidence was found of extracranial lesion and
Figure 1. Neuroimaging. (AeC) Preoperative magnetic resonance imaging T1-weighted sequences with gadolinium (axial, coronal, and sagittal views) revealed a 4.7 4.3 4.5 cm posterior fossa tumor in the left cerebellopontine angle with marked mass effect and moderate hydrocephalus. The tumor demonstrates heterogeneous but prominent enhancement. (DeF) Follow-up magnetic resonance imaging T1-weighted
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intracranial recurrence on brain MRI (Figure 1DeF). She is currently still working as a part-time cleaner at the age of 78. Histopathologic Findings Formalin-fixed, paraffin-embedded hematoxylin-eosinestained sections of the tissue specimen revealed a partially encapsulated tumor composed of duct-like structures admixed with myxochondroid stroma (Figure 2). The ducts were lined by inner luminal cuboidal to columnar epithelial cells and surrounded by an abluminal layer of myoepithelial cells. Occasional mucous cells were also present in the lining epithelium of the ducts. Luminal eosinophilic secretory material was seen (Figure 3A). There was an intimate association of the duct-like structures with the myxochondroid stroma; aggregates of plasmacytoid myoepithelial cells were seen to spread from the environs of the duct-like structures and “melt” into the adjacent stroma (Figure 3B). No carcinomatous change was seen. Tongues of tumor protruded into the capsule, and the capsule was deficient in other areas. Immunohistochemistry demonstrated strong staining of the inner
sequences with gadolinium (axial, coronal, and sagittal views) obtained 8 years after surgery show the tumor has been completely resected with no evidence of recurrence. There was an artifact obscuring some of the right cerebellum secondary to the presence of a ventriculoperitoneal shunt over the right occipital bone.
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myoepithelial nature (Figure 3D), and the luminal ductal epithelial cells were appropriately negative. Because of the unusual intracranial location of the tumor, an additional opinion on the case was sought, and the slides of the pathologic specimens were discussed at a slide seminar in a national neuropathology conference in Sydney, Australia. The consensus review confirmed that it was a benign pleomorphic adenoma. Figure 2. Photomicrograph of the surgical specimen. The pleomorphic tumor is composed of an admixture of duct-like structures and nodules of myxochondroid stroma. A fragment of normal cerebellum is present in the lower right corner. (Hematoxylin-eosin, 20.)
luminal ductal epithelial cells by CAM5.2 (Figure 3C) and epithelial membrane antigen, whereas the cells within the outer layer were predominantly negative. Smooth muscle actin, calponin, and cytokeratin 14 highlighted the outer layer of the ductal structures, confirming their
DISCUSSION Pleomorphic adenoma is the most common benign salivary gland neoplasm.12-14 It is also known as a benign mixed tumor, salivary gland type, with classic histologic composition of a mixture of cells derived from the salivary gland ductal apparatus and stroma.5 In this case, the tumor displayed its typical pleomorphic nature and was characterized by an admixture of ductal epithelial and myoepithelial elements in a variable background stroma that was mucoid and
Figure 3. Photomicrographs of the surgical specimen. (A) Ductal structures lined by an inner luminal layer of cuboidal to columnar epithelial cells and surrounded by an outer layer of myoepithelial cells. Occasional mucous cells are also present in the lining, and luminal eosinophilic secretions are present. (Hematoxylin-eosin, 200.) (B) Typical intimate association of the duct-like structures with the myxochondroid stroma with aggregates of myoepithelial cells “melting” into the adjacent stroma. (Hematoxylin-eosin, 100.) (C) Immunohistochemistry for CAM5.2 demonstrated strong staining of luminal ductal epithelial cells, but the outer layer is predominantly negative. (CAM5.2, 200.) (D) Smooth muscle actin highlighted the outer layer of cells only, confirming its myoepithelial nature. (Smooth muscle actin, 200.)
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cartilaginous. There was no mitotic activity or cytologic or architectural atypia to suggest malignant transformation. Despite extensive investigations, no extracranial source has been identified at 8 years after the operation. Metastasis of a benign pleomorphic adenoma is extremely rare.5,8 The metastatic foci are histologically identical to the primary benign tumor and do not show clinical or histologic features commonly associated with malignant neoplasms.8,14 Tumor recurrence at the primary site characteristically precedes metastasizing pleomorphic adenomas, occurring in approximately 90% of the cases.12-14 Few cases of metastases without local recurrence have been reported in the literature. Bone, lung, and lymph nodes are the most common sites of metastatic disease, but involvement of kidney, liver, CNS, retroperitoneum, and skin has also been rarely reported.7,14 The initial placement of ventriculoperitoneal shunt in this case is based on considerations that the shunting procedure is a safe and effective option to allow gradual normalization of her intracranial hypertension and allow sufficient time for preoperative work-up. The risk of shunt acting as a conduit for extraneural metastases is very low.10,11 In the present case, the patient had no previous surgical history, and extensive radiologic investigations revealed no extracranial lesion. She has been followed for 8 years with satisfactory medical imaging and excellent clinical outcomes. This represents a case of a primary classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site, as primary salivary gland tumors in the intracranial cavity are almost always restricted to the pituitary gland and sellar region because of the presence of Rathke cleft remnants, which may develop into heterotopic salivary gland rests.15 There have been only 4 isolated case reports in the literature of primary salivary gland tumors within the intracranial cavity outside the sellar region.9,16-18 Pleomorphic adenoma is the most common benign salivary gland tumor.12-14 To the best of our knowledge, there has been only 1 previous case report of a primary CNS pleomorphic adenoma, by Yano et al.9 in 1997, who described a posterior cranial fossa pleomorphic adenoma. Their case did not
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.07.059
CASE REPORT LIQUN YANG ET AL.
demonstrate the presence of the classic myxochondroid stroma on histology, and its pathogenesis was not elucidated. There has been no second report on primary CNS pleomorphic adenoma and no previous reports with classic histologic appearances of a pleomorphic adenoma. It is postulated that salivary gland heterotopia is the likely pathogenetic mechanism in the development of rare salivary gland tumors in an unusual intracranial location. One hypothesis is that major and minor salivary glands arise in the embryo from invaginations of the primitive oral epithelium, and the ectopic salivary gland tissue may develop from vestigial structures derived from primitive oral epithelium, such as Rathke pouch, whose cleft remnants can be found in the sellar region.15 Other theories explaining the development of heterotopic salivary gland rests include dislocation of intact seromucous glands from oral cavity and induction of pituitary epithelium by salivary gland mesenchyme accompanying Rathke pouch during embryogenesis (heteroplasia).16 Outside of these locations, intracranial salivary gland rests are rare.16,18 It has been observed that during embryogenesis, thickened patches of ectoderm (known as epibranchial placodes), adjacent to CNs, maintained a close relationship with CN VII.16 It has been hypothesized that some vesicles derived from the epibranchial placodes at the dorsal aspect of the first and second pharyngeal arches may have become dislodged and migrated with the elongation of the facial nerve and its chorda tympani branch to differentiate later into salivary gland tissue in the cerebellopontine angle.16 It has been reported that 26 cases of heterotopic salivary gland tissue and 1 pleomorphic adenoma within the middle ear (also derived from the branchial apparatus) were noted to have mostly an intimate relationship with the facial nerve and chorda tympani branch,19-22 further supporting the aforementioned hypothesis. Additionally, given its proximity to the middle ear, salivary tissue in mastoid air cells may become dislocated and subsequently migrate into posterior cranial fossa.16,18
RARE PRIMARY PLEOMORPHIC ADENOMA IN POSTERIOR FOSSA
CONCLUSIONS Our case study demonstrates that primary pleomorphic adenoma and salivary gland neoplasms may rarely occur in the CNS, and the pathogenesis may involve salivary gland heterotopia. This is a case of a classic pleomorphic adenoma (salivary gland tumor) in an unusual intracranial site and illustrates the complexity of head and neck anatomy and its embryologic assemblage. REFERENCES 1. Cresson DH, Goldsmith M, Askin FB, Reddick RL, Postma DS, Siegal GP. Metastasizing pleomorphic adenoma with myoepithelial cell predominance. Pathol Res Pract. 1990;186:795-800 [discussion: 801-802]. 2. Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G. Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope. 2001;111: 2195-2200. 3. Gnepp DR, Brandwein MS, Henley JD. Salivary and lacrimal glands. In: Gnepp DR, ed. Diagnostic Surgical Pathology of the Head and Neck. Philadelphia, PA: Saunders; 2001:325-430. 4. Som PM, Brandwein MS. Salivary glands: anatomy and pathology. In: Som PM, Curtin HD, eds. Head and Neck Imaging. St Louis, MO: Mosby; 2003: 2067-2076. 5. Sheedy SP, Welker KM, DeLone DR, Gilbertson JR. CNS metastases of carcinoma ex pleomorphic adenoma of the parotid gland. AJNR Am J Neuroradiol. 2006;27:1483-1485. 6. Leonetti JP, Marzo SJ, Petruzzelli GJ, Herr B. Recurrent pleomorphic adenoma of the parotid gland. Otolaryngol Head Neck Surg. 2005;133:319-322. 7. Morrison PD, McMullin JP. A case of metastasizing benign pleomorphic adenoma of the parotid. Clin Oncol. 1984;10:173-176. 8. Fujimura M, Sugawara T, Seki H, Otawara Y, Sakuma T, Nakano Y, et al. Carcinomatous change in the cranial metastasis from a metastasizing mixed tumor of the salivary gland—case report. Neurol Med Chir (Tokyo). 1997;37:546-550. 9. Yano H, Funakoshi T, Shinoda J, Sakai N, Kokuzawa G, Shimokawa K. Primary pleomorphic adenoma in posterior cranial fossa. Brain Tumor Pathol. 1997;14:75-78.
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12. Freeman SB, Kennedy KS, Parker GS, Tatum SA. Metastasizing pleomorphic adenoma of the nasal septum. Arch Otolaryngol Head Neck Surg. 1990;116: 1331-1333. 13. Pitman MB, Thor AD, Goodman ML, Rosenberg AE. Benign metastasizing pleomorphic adenoma of salivary gland: diagnosis of bone lesions by fine-needle aspiration biopsy. Diagn Cytopathol. 1992;8:384-387. 14. Wenig BM, Hitchcock CL, Ellis GL, Gnepp DR. Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis. Am J Surg Pathol. 1992;16:845-858. 15. Hampton TA, Scheithauer BW, Rojiani AM, Kovacs K, Horvath E, Vogt P. Salivary gland-like tumors of the sellar region. Am J Surg Pathol. 1997;21:424-434. 16. Curry B, Taylor CW, Fisher AW. Salivary gland heterotopia: a unique cerebellopontine angle tumor. Arch Pathol Lab Med. 1982;106:35-38. 17. Erdogan S, Rodriguez FJ, Scheithauer BW, AbellAleff PC, Rabin M. Malignant myoepithelioma of cranial dura. Am J Surg Pathol. 2007;31:807-811. 18. Rodriguez F, Scheithauer BW, Ockner DM, Giannini C. Solitary fibrous tumor of the cerebellopontine angle with salivary gland heterotopia: a unique presentation. Am J Surg Pathol. 2004;28:139-142. 19. Enoz M, Suoglu Y. Salivary gland choristoma of the middle ear. Laryngoscope. 2006;116:1033-1034. 20. Hinni ML, Beatty CW. Salivary gland choristoma of the middle ear: report of a case and review of the literature. Ear Nose Throat J. 1996;75:422-424. 21. Lee DK, Kim JH, Cho YS, Chung WH, Hong SH. Salivary gland choristoma of the middle ear in an infant: a case report. Int J Pediatr Otorhinolaryngol. 2006;70:167-170. 22. Saeed YM, Bassis ML. Mixed tumor of the middle ear. A case report. Arch Otolaryngol. 1971;93: 433-434.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 8 May 2016; accepted 15 July 2016
10. Nigim F, Critchlow J, Kasper E. Role of ventriculoperitoneal shunting in patients with neoplasms of the central nervous system. Mol Clin Oncol. 2015;3:1381-1386.
Citation: World Neurosurg. (2016) 93:484.e5-484.e8. http://dx.doi.org/10.1016/j.wneu.2016.07.059
11. Berger MS, Baumeister B, Geyer JR. The risks of metastases from shunting in children with
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